Philippe Thullier

article

Development of a drug delivery system for efficient alveolar delivery of a neutralizing monoclonal antibody to treat pulmonary intoxication to ricin

Renaud Respaud, Denis Marchand, Thibaut Pelat, Kam-Meng Tchou-Wong, more

Journal of Controlled Release > 2016 > 234 > C > 21-32

The high toxicity of ricin and its ease of production have made it a major bioterrorism threat worldwide. There is however no efficient and approved treatment for poisoning by ricin inhalation, although there have been major improvements in diagnosis and therapeutic strategies. We describe the development of an anti-ricin neutralizing monoclonal antibody (IgG 43RCA-G1) and a device for its rapid and...

chapter

Neutralization Tests

Philippe Thullier, Dorothea Thea Sesardic

Antibody Engineering > Antibody Characterization > 705-722

Neutralization tests are performed in vitro, at the cellular level - including on cells in the form of organs - and at the sub-cellular level. They assess the efficacy of antibody fragments, or antibodies, to inhibit critical stages of activities. These activities are generally deleterious to Humans, and neutralization tests mostly apply to viruses and toxins. When isolating recombinant antibodies,...

chapter

Immune Libraries from Nonhuman Primates (NHP)

Thibaut Pelat, Michael Hust, Philippe Thullier

Antibody Engineering > Generation of Antibody Repertoires > 99-114

Libraries constructed from immunised non human primates (NHP; macaques here) are an appealing alternative to human libraries when immunization of Humans is difficult, as is so often the case. These phage-displayed libraries allow to obtain antibody fragments of very high affinities (nano- to picomolar), and diverse epitopes are targeted so that antibodies with the desired activity can be isolated...

article

177. Neutralizing antibodies directed against botulinum neurotoxin types A and B heavy and light chains

Thea Sesardic, Christine Rasetti-Escargueil, Yvonne Liu, Rob Tierney, more

Toxicon > 2015 > 93 > Supplement > S55-S56

article

Isolation of nanomolar scFvs of non-human primate origin, cross-neutralizing botulinum neurotoxins A₁ and A₂ by targeting their heavy chain

Arnaud Avril, Sebastian Miethe, Michel R. Popoff, Christelle Mazuet, more

BMC Biotechnology > 2015 > 15 > 1 > 1-14

Background Botulism is a naturally occurring disease, mainly caused by the ingestion of food contaminated by the botulinum neurotoxins (BoNTs). Botulinum neurotoxins are the most lethal. They are classified among the six major biological warfare agents by the Centers for Disease Control. BoNTs act on the cholinergic motoneurons, where they cleave proteins implicated in acetylcholine vesicle exocytosis...

article

Structural differences of amyloid-β fibrils revealed by antibodies from phage display

Patrick Droste, André Frenzel, Miriam Steinwand, Thibaut Pelat, more

BMC Biotechnology > 2015 > 15 > 1 > 1-13

Background Beside neurofibrillary tangles, amyloid plaques are the major histological hallmarks of Alzheimer’s disease (AD) being composed of aggregated fibrils of β-amyloid (Aβ). During the underlying fibrillogenic pathway, starting from a surplus of soluble Aβ and leading to mature fibrils, multiple conformations of this peptide appear, including oligomers of various shapes and sizes. To further...

article

The Humanness of Macaque Antibody Sequences

Philippe Thullier, Oliver Huish, Thibaut Pelat, Andrew C.R. Martin

Journal of Molecular Biology > 2010 > 396 > 5 > 1439-1450

Chimeric, humanized and human antibodies have successively been exploited as therapeutics because their increasing human (‘self’) character is expected to correspond with decreased immunogenicity, which is critical for their clinical development. Thus, humanness has been inferred to predict antibody immunogenicity. Humanness of antibody variable regions (V-regions) has recently been studied using...

article

Germline Humanization of a Non-human Primate Antibody that Neutralizes the Anthrax Toxin, by in Vitro and in Silico Engineering

Thibaut Pelat, Hugues Bedouelle, Anthony R. Rees, Susan J. Crennell, more

Journal of Molecular Biology > 2008 > 384 > 5 > 1400-1407

Fab 35PA ₈₃ is an antibody fragment of non-human primate origin that neutralizes the anthrax lethal toxin. Human antibodies are usually preferred when clinical use is envisioned, even though their framework regions (FR) may carry mutations introduced during affinity maturation. These hypermutations can be immunogenic and therefore FR that are encoded by human germline genes, encountered in...

article

Improvement of an Antibody Neutralizing the Anthrax Toxin by Simultaneous Mutagenesis of Its Six Hypervariable Loops

Emmanuelle Laffly, Thibaut Pelat, Frédéric Cédrone, Stéphane Blésa, more

Journal of Molecular Biology > 2008 > 378 > 5 > 1094-1103

The enhancement of antibody affinity by mutagenesis targeting only complementarity determining regions has the advantage of respecting the framework regions, which are important for tolerance if clinical use is envisaged. Here, starting from a Fab (antigen-binding fragment; 35PA ₈₃ ) capable of neutralizing the lethal toxin of anthrax and having an affinity of 3.4 nM for its antigen, a phage-displayed...

article

Development and comparison of two immunoassay formats for rapid detection of botulinum neurotoxin type A

Olivier Attrée, Valérie Guglielmo-Viret, Valérie Gros, Philippe Thullier

Journal of Immunological Methods > 2007 > 325 > 1-2 > 78-87

We have evaluated two formats of immunoassays for the rapid detection of Clostridium botulinum neurotoxin type A (BoNT/A), in assay buffer and various matrices (human serum and nasal swabs, fresh milk, sugar, flour and talcum). The two formats, a vertical-flow strip immunochromatography (ICT) and a small disposable immunoaffinity column (IAC), were selected because they are both rapid and readily...

article

A high-affinity macaque antibody Fab with human-like framework regions obtained from a small phage display immune library

Stéphanie Chassagne, Emmanuelle Laffly, Emmanuel Drouet, Francis Hérodin, more

Molecular Immunology > 2004 > 41 > 5 > 539-546

Tetanus toxoid was used as a model antigen for the immunization of Macaca fascicularis. Using peripheral blood as a template, specific Fab-encoding genes were amplified by PCR on the fourth day after the final boost, and cloned in a phagemidic vector (pComb3X) as a small immune library (5x10 ⁵ clones). A high-affinity Fab (K _d =4x10 ^- ¹ ⁰ M), 6-ATT, was isolated from...

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Search results for: Philippe Thullier

Development of a drug delivery system for efficient alveolar delivery of a neutralizing monoclonal antibody to treat pulmonary intoxication to ricin

Neutralization Tests

Immune Libraries from Nonhuman Primates (NHP)

177. Neutralizing antibodies directed against botulinum neurotoxin types A and B heavy and light chains

Isolation of nanomolar scFvs of non-human primate origin, cross-neutralizing botulinum neurotoxins A₁ and A₂ by targeting their heavy chain

Structural differences of amyloid-β fibrils revealed by antibodies from phage display

The Humanness of Macaque Antibody Sequences

Germline Humanization of a Non-human Primate Antibody that Neutralizes the Anthrax Toxin, by in Vitro and in Silico Engineering

Improvement of an Antibody Neutralizing the Anthrax Toxin by Simultaneous Mutagenesis of Its Six Hypervariable Loops

Development and comparison of two immunoassay formats for rapid detection of botulinum neurotoxin type A

A high-affinity macaque antibody Fab with human-like framework regions obtained from a small phage display immune library

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